Upper Klamath Lake (UKL) in southern Oregon has experienced declines in water quality due to excessive nutrient loading. This has led to annual cyanobacterial blooms, primarily of Aphanizomenon flos-aquae (AFA). Benthic invertebrates are important food resources for benthic feeding fishes; however, they can increase autochthonous nutrient cycling in lakes and as a result might be contributing to poor water quality in UKL. This study determined the density and taxonomic richness of benthic invertebrate assemblages in three geographic regions (north, central, and south) and three habitats (littoral, open-water and trench) across UKL. Sediment composition and water quality were also characterized at each of the 21 benthic invertebrate collection sites. Three sampling trips were made from May–July 2013. Mean lake-wide invertebrate density was 12 617 ± 7506 individuals m^-2 (n = 63, based on 189 Ekman grabs) with oligochaetes, chironomids, and leeches representing 97% of all individuals. Mean invertebrate richness per sample was 16 ± 4 (n = 63). Two and three-way repeated measures ANOVAs identified differences in invertebrate densities and richness among regions, habitats, and sampling periods. There were no differences in total density among sampling periods. Total density was higher in littoral compared to open-water habitats, and in the northern region, proximal to all riverine inputs to the lake, compared to the central or southern regions. Although variances were heterogeneous, the number of taxa appeared to differ between habitats and regions.